Plasma Biomarkers of Kidney Tubule Health during Ambulatory AKI and Kidney Function Recovery in SPRINT.

KEY POINTS: AKI frequently occurs in the ambulatory setting, but there are no available tools to distinguish whether kidney function will recover. Plasma biomarkers reflecting kidney tubular injury and dysfunction measured at the time of AKI are associated with nonrecovery in kidney function. Measuring plasma biomarkers of kidney tubule health during ambulatory AKI episodes could be helpful in guiding treatment decisions.

BACKGROUND

AKI frequently occurs in the ambulatory setting, but few tools are available to distinguish whether an individual's kidney function will subsequently recover.

METHODS

We included 652 participants with and without CKD in the Systolic Blood Pressure Intervention Trial who experienced ambulatory AKI, defined as a rise in serum creatinine of ≥0.3 mg/dl from baseline that occurred at the 12- or 24-month study visits. Four plasma biomarkers of kidney tubule health were measured at baseline and when ambulatory AKI was detected: kidney injury molecule-1 (KIM-1), soluble TNF receptor 1 (sTNFR1) and soluble TNF receptor 2, and uromodulin. Multivariable logistic regression models were used to evaluate biomarker associations with subsequent odds of <50% recovery in eGFR (nonrecovery) at 12 months.

RESULTS

The mean age was 70±10 years; eGFR at baseline was 62±25 ml/min per 1.73 m 2 , and there was an eGFR decline of 21.7±12.5 ml/min per 1.73 m 2 at the time ambulatory AKI was detected. When measured at the time of ambulatory AKI, higher KIM-1 (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.14 to 1.73) and sTNFR1 (OR, 2.07; 95% CI, 1.49 to 2.88) and lower uromodulin (OR, 0.77; 95% CI, 0.63 to 0.94) were each associated with eGFR nonrecovery in multivariable models that adjusted for eGFR and albuminuria. In models that included all four plasma biomarkers, KIM-1 and sTNFR1 remained jointly associated with eGFR nonrecovery.

CONCLUSIONS

Among hypertensive adults with ambulatory AKI, plasma biomarkers reflecting impaired kidney tubule health measured at the time of ambulatory AKI are associated with subsequent nonrecovery in kidney function.